Amarin Corporation plc (NASDAQ:AMRN), a pharmaceutical company
focused on improving cardiovascular health, today announced that,
as planned, it submitted a supplemental new drug application (sNDA)
to the U.S. Food and Drug Administration (FDA) seeking an expanded
indication for its lead product, Vascepa® (icosapent ethyl)
capsules, based on the landmark REDUCE-IT™ cardiovascular outcomes
study1, 2. As is typical, while the FDA acknowledged receipt of the
sNDA submission, at this stage FDA has not yet communicated to
Amarin the intended timing of its review. Unless and until the
company learns otherwise in communications from the FDA, the review
timing is typically communicated within 60 to 74 days of the FDA’s
receipt of an sNDA. Amarin is operating under the assumption that
the sNDA will be reviewed on a standard review clock of ten months
resulting in a PDUFA date near the end of January 2020.
"This submission is another step forward toward
our goal to help address the risk of cardiovascular disease," said
John F. Thero, president and chief executive officer of Amarin."
The REDUCE-IT results support that approximately 1 fewer major
cardiovascular adverse event would occur on average for every 6
patients treated with Vascepa for 5 years on top of statin therapy
compared to placebo1. This unprecedented result beyond cholesterol
management presents an important new preventative care opportunity
for millions of patients."
As is typical for a trial of this size, the
electronic sNDA submission consists of over 5 million pages of
information regarding Vascepa, including data from over 35,000
patient years of study in REDUCE-IT. A total events analysis from
the REDUCE-IT study was recently published online in the Journal of
the American College of Cardiology1, and the primary results of the
REDUCE-IT study were previously published in The New England
Journal of Medicine2. In REDUCE-IT, Vascepa provided a 25% relative
risk reduction compared to placebo in the first occurrence of a
major adverse CV event (MACE) in the intent-to-treat population
consisting of a composite of cardiovascular death, nonfatal
myocardial infarction (MI or heart attack), nonfatal stroke,
coronary revascularization (procedures such as stents and by-pass)
and unstable angina requiring hospitalization. For total (first and
subsequent) cardiovascular events, Vascepa provided a statistically
significant 30% risk reduction compared to placebo in the
statin-treated patient population studied in REDUCE-IT. REDUCE-IT
was performed under a Special Protocol Assessment (SPA) with the
FDA. In REDUCE-IT, adverse events occurring with Vascepa use
at greater than 5% and greater than placebo were: peripheral
edema (6.5% Vascepa versus 5.0%), although there was no increase in
the rate of heart failure in Vascepa patients; constipation (5.3%
Vascepa versus 3.6%), although mineral oil, as used as placebo, is
known to lower constipation; and atrial fibrillation (5.3% Vascepa
versus 3.9%), although there were reductions in rates of cardiac
arrest, sudden death and myocardial infarctions observed in Vascepa
patients. More information on safety data associated with
REDUCE-IT is provided below.
Amarin has previously expressed that it believes
it is likely that there will be an Advisory Committee (AdCom)
meeting organized by the FDA in conjunction with its review of the
expanded label for Vascepa sought in its sNDA based on the landmark
results of the REDUCE-IT cardiovascular outcomes study and the very
large patient population that Vascepa could potentially address.
However, the FDA determination as to whether or not there will be
an AdCom has not yet been communicated to Amarin. Typically, the
FDA does not communicate such a decision until it has had the
opportunity to substantially review the sNDA.
About Amarin
Amarin Corporation plc. is a rapidly growing,
innovative pharmaceutical company focused on developing
therapeutics to improve cardiovascular health. Amarin’s product
development program leverages its extensive experience in
polyunsaturated fatty acids and lipid science. Vascepa (icosapent
ethyl) is Amarin's first FDA-approved drug and is available by
prescription in the United States, Lebanon and the United Arab
Emirates. Amarin’s commercial partners are pursuing additional
regulatory approvals for Vascepa in Canada, China and the Middle
East. For more information about Amarin, visit
www.amarincorp.com.
About REDUCE-IT
REDUCE-IT2, an 8,179-patient cardiovascular
outcomes study, was completed in 2018. REDUCE-IT was the first
multinational cardiovascular outcomes study that evaluated the
effect of prescription pure EPA therapy as an add-on to statins in
patients with high cardiovascular risk who, despite stable statin
therapy, had elevated triglyceride levels (at least 135 mg/dL). A
large portion of the male and female patients enrolled in this
outcomes study were diagnosed with type 2 diabetes.
More information on the REDUCE-IT study results
can be found at www.amarincorp.com.
About Cardiovascular
Disease
Worldwide, cardiovascular disease (CVD) remains
the #1 killer of men and women. In the United States CVD leads to
one in every three deaths – one death approximately every 38
seconds – with annual treatment cost in excess of $500 billion.3,
4
Multiple primary and secondary
prevention trials have shown a significant reduction of 25% to
35% in the risk of cardiovascular
events with statin therapy, leaving significant
persistent residual risk despite the achievement of target LDL-C
levels.5
Beyond the cardiovascular risk associated with
LDL-C, genetic, epidemiologic, clinical and real-world data suggest
that patients with elevated triglycerides (TG) (fats in the blood),
and TG-rich lipoproteins, are at increased risk for cardiovascular
disease. 6, 7, 8, 9
About Vascepa (icosapent ethyl)
Capsules
Vascepa (icosapent ethyl) capsules are a
single-molecule prescription product consisting of the omega-3 acid
commonly known as EPA in ethyl-ester form. Vascepa is not fish oil,
but is derived from fish through a stringent and complex
FDA-regulated manufacturing process designed to effectively
eliminate impurities and isolate and protect the single molecule
active ingredient from degradation. Vascepa, known in scientific
literature as AMR101, has been designated a new chemical entity by
the FDA. Amarin has been issued multiple patents internationally
based on the unique clinical profile of Vascepa, including the
drug’s ability to lower triglyceride levels in relevant patient
populations without raising LDL-cholesterol levels.
Indication and Usage Based on Current
FDA-Approved Label (not including REDUCE-IT results)
- Vascepa (icosapent ethyl) is
indicated as an adjunct to diet to reduce triglyceride (TG) levels
in adult patients with severe (≥500 mg/dL)
hypertriglyceridemia.
- The effect of Vascepa on the risk
for pancreatitis and cardiovascular mortality and morbidity in
patients with severe hypertriglyceridemia has not been
determined.
Important Safety Information for Vascepa Based
on Current FDA-Approved Label (not including REDUCE-IT results)
(Includes Data from Two 12-Week Studies (n=622) (MARINE and ANCHOR)
of Patients with Triglycerides Values of 200 to 2000 mg/dL)
- Vascepa is contraindicated in
patients with known hypersensitivity (e.g., anaphylactic reaction)
to Vascepa or any of its components.
- In patients with hepatic
impairment, monitor ALT and AST levels periodically during
therapy.
- Use with caution in patients with
known hypersensitivity to fish and/or shellfish.
- The most common reported adverse
reaction (incidence >2% and greater than placebo) was arthralgia
(2.3% for Vascepa, 1.0% for placebo). There was no reported adverse
reaction >3% and greater than placebo.
- Adverse events and product
complaints may be reported by calling 1-855-VASCEPA or the FDA at
1-800-FDA-1088.
- Patients receiving treatment with
Vascepa and other drugs affecting coagulation (e.g., anti-platelet
agents) should be monitored periodically.
- Patients should be advised to
swallow Vascepa capsules whole; not to break open, crush, dissolve,
or chew Vascepa.
FULL VASCEPA PRESCRIBING INFORMATION CAN BE
FOUND AT WWW.VASCEPA.COM.
Important Safety Information for Vascepa based on REDUCE-IT, as
previously reported in The New England Journal of Medicine2
publication of the primary results of the REDUCE-IT study:
- Excluding the major adverse cardiovascular events (MACE)
results described above, overall adverse event rates in REDUCE-IT
were similar across the statin plus Vascepa and the statin plus
placebo treatment groups.
- There were no significant differences between treatments in the
overall rate of treatment emergent adverse events or serious
adverse events leading to withdrawal of study drug.
- There was no serious adverse event (SAE) occurring at a
frequency of >2% which occurred at a numerically higher rate in
the statin plus Vascepa treatment group than in the statin plus
placebo treatment group.
- Adverse events (AEs) occurring in 5% or greater of patients and
more frequently with Vascepa than placebo were:
- peripheral edema (6.5% Vascepa patients versus 5.0% placebo
patients), although there was no increase in the rate of heart
failure in Vascepa patients
- constipation (5.4% Vascepa patients versus 3.6% placebo
patients), although mineral oil, as used as placebo, is known to
lower constipation, and
- atrial fibrillation (5.3% Vascepa patients versus 3.9% placebo
patients), although there were reductions in rates of cardiac
arrest, sudden death and myocardial infarctions observed in Vascepa
patients
- There were numerically more SAEs related to bleeding in the
statin plus Vascepa treatment group although overall rates were low
with no fatal bleeding observed in either group and no significant
difference in adjudicated hemorrhagic stroke or serious central
nervous system or gastrointestinal bleeding events between
treatments.
- In summary, Vascepa was well tolerated with a safety profile
generally consistent with clinical experience associated with
omega-3 fatty acids and current FDA-approved labeling of such
products.
Vascepa has been approved for use by the United
States Food and Drug Administration (FDA) as an adjunct to diet to
reduce triglyceride levels in adult patients with severe (≥500
mg/dL) hypertriglyceridemia. FDA has not reviewed and opined on a
supplemental new drug application related to REDUCE-IT. FDA has not
reviewed the information herein or determined whether to approve
Vascepa for use to reduce the risk of MACE. Nothing in this press
release should be construed as promoting the use of Vascepa in any
indication that has not been approved by the FDA.
Important Cautionary Information About
These Data
Further REDUCE-IT data assessment and data
release could yield additional useful information to inform greater
understanding of the trial outcome. Further detailed data
assessment by Amarin and regulatory authorities will
continue and take several months to complete and record. The final
evaluation of the totality of the efficacy and safety data from
REDUCE-IT may include some or all of the following, as well as
other considerations: new information affecting the degree of
treatment benefit on studied endpoints; study conduct and data
robustness, quality, integrity and consistency; additional safety
data considerations and risk/benefit considerations; consideration
of REDUCE-IT results in the context of other clinical studies.
Recurrent event analyses for the total primary
endpoint events and for the total key secondary endpoint in
REDUCE-IT as published in the Journal of the American College of
Cardiology1 were conducted using a series of statistical models.
These analyses were tertiary or exploratory endpoints; most of the
models used were prespecified and one was post hoc. Each recurrent
event statistical model has inherent strengths and weaknesses, with
no single model considered definitive or outperforming the other
models, and this is an evolving field of science. Nonetheless,
results from the total primary and total key secondary endpoint
events analyses are consistent across the various recurrent event
statistical models and are also consistent with the original
primary and secondary endpoint results. Together, the REDUCE-IT
recurrent event analyses and the original primary and key secondary
endpoint analyses support the robustness of the clinical benefit of
Vascepa therapy in reducing cardiovascular risk.
Forward-Looking Statements
This press release contains forward-looking
statements, including expectations regarding FDA review and related
timelines, that REDUCE-IT results could lead to a new treatment
paradigm in the patient population studied and present an important
new preventative care opportunity for millions of patients. These
forward-looking statements are not promises or guarantees and
involve substantial risks and uncertainties. In addition, Amarin's
ability to effectively commercialize Vascepa will depend in part on
its ability to continue to effectively finance its business,
efforts of third parties, its ability to gain regulatory approvals,
create market demand for Vascepa through education, marketing and
sales activities, to achieve market acceptance of Vascepa, to
receive adequate levels of reimbursement from third-party payers,
to develop and maintain a consistent source of commercial supply at
a competitive price, to comply with legal and regulatory
requirements in connection with the sale and promotion of Vascepa
and to maintain patent protection for Vascepa. Among the factors
that could cause actual results to differ materially from those
described or projected herein include the following: uncertainties
associated generally with research and development, clinical trials
and related regulatory approvals; the risk that sales may not meet
expectations and related cost may increase beyond expectations; the
risk that patents may not be upheld in patent litigation and
applications may not result in issued patents sufficient to protect
the Vascepa franchise. A further list and description of these
risks, uncertainties and other risks associated with an investment
in Amarin can be found in Amarin's filings with the U.S. Securities
and Exchange Commission, including its most recent annual report on
Form 10-K. Existing and prospective investors are cautioned not to
place undue reliance on these forward-looking statements, which
speak only as of the date hereof. Amarin undertakes no obligation
to update or revise the information contained in this press
release, whether as a result of new information, future events or
circumstances or otherwise.
Availability of Other Information About
Amarin
Investors and others should note that Amarin
communicates with its investors and the public using the company
website (www.amarincorp.com), the investor relations website
(investor.amarincorp.com), including but not limited to investor
presentations and investor FAQs, Securities and Exchange Commission
filings, press releases, public conference calls and webcasts. The
information that Amarin posts on these channels and websites could
be deemed to be material information. As a result, Amarin
encourages investors, the media, and others interested in Amarin to
review the information that is posted on these channels, including
the investor relations website, on a regular basis. This list of
channels may be updated from time to time on Amarin’s investor
relations website and may include social media channels. The
contents of Amarin’s website or these channels, or any other
website that may be accessed from its website or these channels,
shall not be deemed incorporated by reference in any filing under
the Securities Act of 1933.
References
1 Bhatt DL, Steg PG, Miller M, et al.
Effects of Icosapent Ethyl on Total Ischemic Events: From
REDUCE-IT. J Am Coll Cardiol 2019. epub ahead of
print.http://www.onlinejacc.org/content/early/2019/03/01/j.jacc.2019.02.0322 Bhatt
DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with
Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med
2019;380:11-22.3 American Heart Association. 2018.
Disease and Stroke Statistics-2018 Update.4 American
Heart Association. 2017. Cardiovascular disease: A costly burden
for America projections through 2035.5 Ganda OP, Bhatt
DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy
in hypertriglyceridemia management. J Am Coll Cardiol.
2018;72(3):330-343.6 Budoff M. Triglycerides and
triglyceride-rich lipoproteins in the causal pathway of
cardiovascular disease. Am J Cardiol.
2016;118:138-145.7 Toth PP, Granowitz C, Hull M, et al.
High triglycerides are associated with increased cardiovascular
events, medical costs, and resource use: A real-world
administrative claims analysis of statin-treated patients with high
residual cardiovascular risk. J Am Heart Assoc.
2018;7(15):e008740.8 Nordestgaard BG. Triglyceride-rich
lipoproteins and atherosclerotic cardiovascular disease - New
insights from epidemiology, genetics, and biology. Circ Res.
2016;118:547-563.9 Nordestgaard BG, Varbo A.
Triglycerides and cardiovascular disease. Lancet.
2014;384:626–635.
Amarin Contact Information
Investor Relations:Elisabeth SchwartzInvestor Relations and
Corporate Communications Amarin Corporation plc In U.S.: +1
(908) 719-1315 investor.relations@amarincorp.com (investor
inquiries)PR@amarincorp.com (media inquiries)
Lee M. Stern Solebury Trout In U.S.: +1 (646)
378-2992lstern@soleburytrout.com
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